Effect of human cerebrospinal fluid sampling frequency on amyloid-β levels

Jinhe Li, Daniel A. Llano, Teresa Ellis, David Leblond, Anahita Bhathena, Stanford S. Jhee, Larry Ereshefsky, Robert Lenz, Jeffrey F. Waring

Research output: Contribution to journalArticlepeer-review

Abstract

Background: β-amyloid peptide (Aβ) is associated with neurodegeneration in Alzheimer's disease. Emerging evidence indicates that Aβ levels in cerebrospinal fluid (CSF) may serve as an early clinical biomarker for evaluating pharmacological activity of new drug candidates targeting Aβ production or Aβ clearance. Therefore, it is critical to understand whether intrasubject levels of CSF Aβ are consistent between sampling intervals to determine whether Aβ can be used as a pharmacodynamic biomarker for drug candidates. Previous studies have produced seemingly conflicting observations for the intrasubject stability of CSF Aβ levels; we attempt to reconcile these conflicting observations. Methods: The current study examined the Aβ levels in CSF collected with various sampling frequencies from three clinical studies conducted in healthy young or elderly subjects at the same investigative site for the purpose of designing future studies. Results: The results suggest that CSF sampling frequency and/or sampling volume contributes to intrasubject variability in CSF Aβ levels, and that lowering the CSF sampling frequency may help minimize this effect. Conclusion: These results will help guide clinical trial design for Alzheimer's disease therapy.

Original languageEnglish (US)
Pages (from-to)295-303
Number of pages9
JournalAlzheimer's and Dementia
Volume8
Issue number4
DOIs
StatePublished - Jul 2012
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Amyloid
  • Biomarker
  • Cerebrospinal fluid
  • Clinical trial

ASJC Scopus subject areas

  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Health Policy
  • Developmental Neuroscience
  • Epidemiology

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